This project is innovative in both the questions to be addressed and many of the tools to be employed. Mechanotransduction by integrin-dependent adhesions is a major area of current interest but detailed molecular mechanisms are pooriy understood. What stands out compared to ether studies is that we propose to study these phenomena in the context of high resolution analysis of cytoskeletal and receptor dynamics. This combination is highly nevel and offers major opportunities for deeper molecular understanding of what is, in essence, a dynamic phenomenon. Additionally, numerous technical innovations will be combined in this study. These include analysis of mutants of integrins and cytoskeletal proteins, a state of the art, high resolution EM technique, novel materials, nevel biosensors, and nevel imaging and data analysis methods. The application therefore contains mulfiple innovative aspects that take it far beyond current work.